PROJECT SUMMARY: Lung cancer is one of the most aggressive and common malignancies world-wide. While surgical resection remains the best chance of cure, only 20% of patients are eligible for surgery. The remaining patients are managed with combinations of radiotherapy and chemotherapy and more recently with less invasive stereotactic radiotherapy and percutaneous thermal ablation. Percutaneous radio-frequency ablation (RFA) or microwave ablation are cost-effective treatment options for unresectable tumors. This minimally invasive approach, though effective for treatment of some stage 1 and 2 non-small cell lung carcinomas either alone or in combination with other therapies, suffer in terms of their ability to create thermal destruction of the tumors with sufficient margin without risking serious adverse events like pneumothorax and collateral injury. The goal of this proposal is to refine the design of a full-length, endobronchial RFA system that is compatible with the working channel of a bronchoscope and can achieve thermal ablation of peripheral nodules 2-3 cm in diameter with minimal risk of pneumothorax. Our innovative approach overcomes past attempts of using RFA to make large lesions without crossing the airway by combining, in a single device, air aspiration and irrigation flow to increase lesion together with a custom RF generator algorithm. Our device is designed to be compatible with contemporary navigation systems and could be used in conjunction with currently available tools for lung tumor biopsy or imaging (e.g., radial EBUS). This project will be completed in several sequential stages. For this Phase I SBIR we will demonstrate proof of technical concept that our innovative approach to RFA with a device completely in the airway can make large lesions in preclinical models without causing acute pneumothorax despite close proximity to the pleura. Successful completion of the specific aims will lead to the development of a clinical-grade device that can be validated and verified with modern navigation tools to safely and effectively ablate tumor phantoms planned for Phase II of the project.